The present invention relates to new pharmaceutical agents for prophylaxis or treatment of diabetes mellitus comprising an insulin sensitizer and a diuretic, said diuretic having the activity of preventing or treating edema caused by the insulin sensitizer.
It is known that insulin sensitizers are useful as agents for the prevention and/or treatment of diabetes mellitus. However, it is also known that insulin sensitizers sometimes elicit adverse events such as increase in heart-weight, cardiac enlargement, edema, hydrothorax and the like, when used clinically. These adverse events are considered to be associated with retention of body fluid due to increased sensitivity to insulin. On the other hand, diuretics are agents that promote excretion of excess body fluid (hydrothorax, plasma, etc.) as urine. When diuretics are co-administered with insulin sensitizers, adverse events such as increase in heart-weight, cardiac enlargement, edema, hydrothorax, which are related to retention of body fluid, are expected to be suppressed by preventing such retention.
Loop diuretics are known to produce more potent diuretic action than other diuretics. On the other hand, epithelial Na+ channel (ENaC) blockers are used with a combination of other diuretics, because their diuretic action is mild.